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1.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2942-2948, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467684

RESUMO

To systematically search and sort out the clinical randomized controlled trial(RCT) on the prevention and treatment of acute cerebral infarction with traditional Chinese medicine(TCM) by using the method of evidence map, and to understand the evidence distribution of related studies. CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Cochrane Library and Web of Science were retrieved from January 2016 to September 2020, and literatures related to the prevention and treatment of acute cerebral infarction with traditional Chinese medicine were included. Text description combined with table and bubble chart were used to analyze the distribution characteristics of evidence. A total of 1 102 clinical articles in recent five years were retrieved. The annual trend of clinical study publication, study size, TCM therapy category and main scheme, and study literature quality were analyzed. We find that TCM treatment of acute cerebral infarction has become a hot topic of clinical research, the number of literature showed a trend of increased year by year, various means of intervention of TCM in the treatment of the advantages of increasingly highlight. Follow-up clinical research should highlight the characteristics of TCM: in the analysis of outcome indicators; increase the neuropsychological patients after stroke and cognitive ability, and the theory of combined treatment of TCM disease when thoughts; At the same time, the quality of clinical research needs to be improved. At present, there is still a lack of unified standards for the production of evidence map. This study is the first to explore the application of evidence map to summarize and display the clinical research status of TCM treatment of acute cerebral infarction, and combine it with the setting of priority areas of TCM clinical research, so as to provide a reference basis for determining the priority topic selection of TCM treatment optimization research.


Assuntos
Isquemia Encefálica , Medicamentos de Ervas Chinesas , Acidente Vascular Cerebral , Infarto Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa , Acidente Vascular Cerebral/tratamento farmacológico
2.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2949-2962, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467685

RESUMO

To analyze the use of outcome indicators of randomized controlled trial(RCT) of acupuncture in the treatment of acute ischemic stroke in recent three years, so as to provide a basis for building a study on the core outcome indicators for the treatment of acute ischemic stroke with acupuncture. The RCTs of acupuncture treatment for acute ischemic stroke in recent three years were collec-ted through computer retrieval of eight Chinese and English databases and two clinical trial registries at home and abroad. Literature was screened out, and data was extracted. Risk of assessment bias tool Cochrane 6.1 was used for bias risk assessment, outcome indicators were summarized and analyzed. A total of 47 RCTs were included, and 3 studies were trials registration scheme. Outcome indicators were divided into 6 categories according to functional attributes, namely physical symptoms/signs, physical and chemical examination, quality of life, traditional Chinese medicine symptoms/syndromes, safety events and long-term prognosis. The study found that in addition to the common problems in previous studies covered by the status quo of outcome indicators selection of RCT of acupuncture in the treatment of acute ischemic stroke, there were also the other problems as follows: emphasis on macroscopic efficacy indicators but neglect of acupuncture specific indicators, lack of characteristic indicators and economic indicators of traditional Chinese medicine therapy, and unification of indicators measurement tool and measurement time point. In the future, the outcome indicators set for the treatment of acute ischemic stroke with acupuncture shall be established, and the core outcome indicators set shall be in line with the characteristics of traditional Chinese medicine treatment.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/terapia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
3.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2963-2971, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467686

RESUMO

To overview the systematic reviews of Panax notoginseng saponins in the treatment of acute cerebral infarction. CNKI, CBM, Wanfang, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to collect the systematic reviews of the efficacy of P. notoginseng saponins in the treatment of acute cerebral infarction. The retrieval time was from the time of database establishment to January 2021. After two researchers independently screened out the literature and extracted the data, AMSTAR-2 scale was used to evaluate the methodological quality of the included systematic reviews, GRADE system was used to grade the quality of evidences of the outcome indicators, and the efficacy evaluation was summarized. A total of 5 systematic reviews were included. AMSTAR-2 evaluation results showed that 3 items were relatively complete, while 4 items had a poor overall quality. P. notoginseng saponins combined with conventional Western medicine therapy was superior to single conventional therapy in the recovery of neurological function, enhancement of the total effective rate in clinic, and improvement of activities of daily living. GRADE evaluation results showed that the quality of evidence was from low quality to very low quality. In conclusion, in the treatment of acute cerebral infarction, P. notoginseng saponins can improve the clinical efficacy, with a good safety but a not high methodological quality and a low evidence quality. It is suggested that high-quality clinical studies shall be further carried out to provide evidence-based basis for the application of P. notoginseng saponins in the treatment of acute cerebral infarction.


Assuntos
Panax notoginseng , Saponinas , Atividades Cotidianas , Infarto Cerebral/tratamento farmacológico , Humanos , Revisões Sistemáticas como Assunto
4.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2972-2983, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467687

RESUMO

There have been many clinical trials, systematic reviews/Meta-analysis proving that Xingnaojing Injection has a good clinical efficacy in treatment of cerebral ischaemic stroke, but with fewer comprehensive descriptions. In this study, an overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treating cerebral ischaemic stroke was performed to provide current situation of evidences and basis for clinical practice. CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science were retrieved through computers. A total of 6 literatures were included in this study. By AMSTAR-2 checklist and GRADE, the quality of included systematic reviews and the efficacy of Xingnaojing Injection were evaluated. The results of AMSTAR-2 checklist showed an extremely low quality for all of the 6 systematic reviews. According to the results of GRADE evaluation, among 55 outcomes, there were 2 outcomes with a medium quality, 4 outcomes with a low quality and 49 outcomes with an extremely low quality. The 6 systematic reviews reached a consistent conclusion that Xingnaojing Injection was effective in the treatment of cerebral ischaemic stroke. This therapy could improve the total efficacy, neurological deficit scores, hemodynamic and hemodynamic parameters. However, the methodolo-gical quality of all literatures was extremely low. The evidence levels of outcomes were between extremely low to medium. The effectiveness of Xingnaojing Injection in the treatment of cerebral ischaemic stroke still needs to be further verified by more high-quality studies. In the future, relevant clinical studies and systematic reviews/Meta-analysis shall be carried out in a strict accordance with relevant regulations.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Revisões Sistemáticas como Assunto
5.
Emerg Microbes Infect ; : 1-28, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34511027

RESUMO

ABSTRACTEnterovirus A71 (EV-A71) can cause hand, foot and mouth disease with neurological and systemic complications, most frequently affecting children and infants. We describe a cis-acting replication element (cre) with a conserved stem-loop structure within the EV-A71 2C-coding region. By site-directed mutagenesis and reverse genetics using the EV-A71 full-length genome and the EV-A71 replicon containing the firefly luciferase reporter gene in place of the P1 region, the stem-loop structure and the AAACA in the loop of the cre were confirmed to be required for the EV-A71 replication phenotype. EV-A71 genomes containing a mutation at the first or third A residue of AAACA could not be recovered. Insertion of a wild-type cre from EV-A71 or poliovirus in the 5'UTR led to successful recovery of the replication of nonviable mutants. Furthermore, the cre mutants showed lower binding capacity with the host cellular factor IGF2BP2, knockdown of which resulted in a significant decrease in EV-A71 production. All the available evidence shows the location independence but functional importance of the interaction of the cre with the cellular host for efficient production of EV-A71, contributing to the growing body of knowledge regarding picornavirus cres.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34494355

RESUMO

BACKGROUND: Five definitions of peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) are used in clinical trials; their clinical relevance in coronary bifurcation stenting remains unclear. OBJECTIVES: To understand the correlation between PMI and mortality in bifurcation lesions from the DKCRUSH studies. METHODS: PMI was defined using serum creatine kinase-myocardial band (CK-MB) values within 48 h of PCI according to the SYNTAX, Fourth Universal Definition of MI (4th UDMI), ISCHEMIA, SCAI, and EXCEL definitions. Overall, 1300 patients with both CK and CK-MB measurements pre- and post-stenting were evaluated. The association of each PMI type and all-cause death or cardiac death at a median of 5.58 years of follow-up was analyzed using Cox regression. RESULTS: In total, 56 (4.3%) patients had PMI. According to SYNTAX, 4th UDMI or ISCHEMIA, SCAI, and EXCEL definitions, PMI occurred in 21 (1.6%), 56 (4.3%), 29 (2.2%), and 32 (2.5%) patients, respectively. All definitions were significantly correlated with unadjusted mortality at the end of follow-up but not at 30 days or 1-year after stenting. PMI using SYNTAX, SCAI, and EXCEL definitions rather than 4th UDMI definition was strongly associated with adjusted all-cause death. By adjusted analysis, PMI according to 4th UDMI, SCAI, and EXCEL definitions but not SYNTAX definition was positively correlated with cardiac death at a median of 5.58 years of follow-up. CK-MB ≥ 5 x UNL strongly enhanced the correlation of CK-MB values with mortality. CONCLUSIONS: PMI rate varies with the definition following stenting for bifurcation lesions. PMI defined by SCAI and EXCEL definitions is strongly correlates with adjusted all-cause and cardiac death.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34494820

RESUMO

Enhancing the operating temperature of concentrating solar power systems is a promising way to obtain higher system efficiency and thus enhance their competitiveness. One major barrier is the unavailability of suitable solar absorber materials for operation at higher temperatures. In this work, we report on a new high-temperature absorber material by combining Ti2AlC MAX phase material and iron-cobalt-chromite spinel coating/paint. This durable material solution exhibits excellent performance, passing the thermal stability test in an open-air environment at a temperature of 1250 °C for 400 h and at 1300 °C for 200 h. The results show that the black spinel coating can offer a stable high solar absorptivity in the range of 0.877-0.894 throughout the 600 h test under high temperatures. These solar absorptivity values are even 1.6-3.3% higher than that for the sintered SiC ceramic that is a widely used solar absorber material. Divergence of solar absorptivity during these relatively long testing periods is less than 1.1%, indicating remarkable stability of the absorber material. Furthermore, considering the simple application process of the coating/painting utilizing a brush followed by curing at relatively low temperatures (room temperature, 95 and 260 °C in sequence), this absorber material shows the potential for large-scale, high-temperature solar thermal applications.

8.
JAMA Cardiol ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495297

RESUMO

Importance: Early-onset atrial fibrillation (AF) can be the initial manifestation of a more serious underlying inherited cardiomyopathy or arrhythmia syndrome. Objective: To examine the results of genetic testing for early-onset AF. Design, Setting, and Participants: This prospective, observational cohort study enrolled participants from an academic medical center who had AF diagnosed before 66 years of age and underwent whole genome sequencing through the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine program. Participants were enrolled from November 23, 1999, to June 2, 2015. Data analysis was performed from October 24, 2020, to March 11, 2021. Exposures: Rare variants identified in a panel of 145 genes that are included on cardiomyopathy and arrhythmia panels used by commercial clinical genetic testing laboratories. Main Outcomes and Measures: Sequencing data were analyzed using an automated process followed by manual review by a panel of independent, blinded reviewers. The primary outcome was classification of rare variants using American College of Medical Genetics and Genomics criteria: benign, likely benign, variant of undetermined significance, likely pathogenic, or pathogenic. Disease-associated variants were defined as pathogenic/likely pathogenic variants in genes associated with autosomal dominant or X-linked dominant disorders. Results: Among 1293 participants (934 [72.2%] male; median [interquartile range] age at enrollment, 56 [48-61] years; median [interquartile range] age at AF diagnosis, 50 [41-56] years), genetic testing identified 131 participants (10.1%) with a disease-associated variant, 812 (62.8%) with a variant of undetermined significance, 92 (7.1%) as heterozygous carriers for an autosomal recessive disorder, and 258 (20.0%) with no suspicious variant. The likelihood of a disease-associated variant was highest in participants with AF diagnosed before the age of 30 years (20 of 119 [16.8%; 95% CI, 10.0%-23.6%]) and lowest after the age of 60 years (8 of 112 [7.1%; 95% CI, 2.4%-11.9%]). Disease-associated variants were more often associated with inherited cardiomyopathy syndromes compared with inherited arrhythmias. The most common genes were TTN (n = 38), MYH7 (n = 18), MYH6 (n = 10), LMNA (n = 9), and KCNQ1 (n = 8). Conclusions and Relevance: In this cohort study, genetic testing identified a disease-associated variant in 10% of patients with early-onset AF (the percentage was higher if diagnosed before the age of 30 years and lower if diagnosed after the age of 60 years). Most pathogenic/likely pathogenic variants are in genes associated with cardiomyopathy. These results support the use of genetic testing in early-onset AF.

9.
Molecules ; 26(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34500587

RESUMO

DNA methyltransferases (DNMTs) including DNMT1 are a conserved family of cytosine methylases that play crucial roles in epigenetic regulation. The versatile functions of DNMT1 rely on allosteric networks between its different interacting partners, emerging as novel therapeutic targets. In this work, based on the modeling structures of DNMT1-ubiquitylated H3 (H3Ub)/ubiquitin specific peptidase 7 (USP7) complexes, we have used a combination of elastic network models, molecular dynamics simulations, structural residue perturbation, network modeling, and pocket pathway analysis to examine their molecular mechanisms of allosteric regulation. The comparative intrinsic and conformational dynamics analysis of three DNMT1 systems has highlighted the pivotal role of the RFTS domain as the dynamics hub in both intra- and inter-molecular interactions. The site perturbation and network modeling approaches have revealed the different and more complex allosteric interaction landscape in both DNMT1 complexes, involving the events caused by mutational hotspots and post-translation modification sites through protein-protein interactions (PPIs). Furthermore, communication pathway analysis and pocket detection have provided new mechanistic insights into molecular mechanisms underlying quaternary structures of DNMT1 complexes, suggesting potential targeting pockets for PPI-based allosteric drug design.

11.
Hum Immunol ; 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34404545

RESUMO

BACKGROUND AND PURPOSE: Currently there are no widely accepted guidelines for chimerism analysis testing in hematopoietic cell transplantation (HCT) patients. The objective of this review is to provide a practical guide to address key aspects of performing and utilizing chimerism testing results. In developing this guide, we conducted a survey of testing practices among laboratories that are accredited for performing engraftment monitoring/chimerism analysis by either the American Society for Histocompatibility & Immunogenetics (ASHI) and/or the European Federation of Immunogenetics (EFI). We interpreted the survey results in the light of pertinent literature as well as the experience in the laboratories of the authors. RECENT DEVELOPMENTS: In recent years there has been significant advances in high throughput molecular methods such as next generation sequencing (NGS) as well as growing access to these technologies in histocompatibility and immunogenetics laboratories. These methods have the potential to improve the performance of chimerism testing in terms of sensitivity, availability of informative genetic markers that distinguish donors from recipients as well as cost. SUMMARY: The results of the survey revealed a great deal of heterogeneity in chimerism testing practices among participating laboratories. The most consistent response indicated monitoring of engraftment within the first 30 days. These responses are reflective of published literature. Additional clinical indications included early detection of impending relapse as well as identification of cases of HLA-loss relapse.

12.
Ground Water ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388266

RESUMO

Numerous continuous conduits exist in rock masses. These conduits affect the specific discharge distribution of the bulk rock mass. In this study, a modified theoretical model is presented to explore the specific discharge distribution in bedrock with an axisymmetric infilled conduit. The movement of fluid in the free region abides by the Navier-Stokes equation, and the seepage flow in the filling and rock regions complies with the Brinkman-extended Darcy equation. The analytical solution for the specific discharge distribution is derived by requiring flow continuity at the domain interface. This solution can be reduced to Darcy's law and Poiseuille's law. Sensitivity analysis shows that both the relative aperture of the free region and the permeability of the filling or rock regions positively influence the specific discharge. The specific discharge distribution curves seem to have an intersection for different porosity values. Moreover, the width of the transition layer where the porous media flow differs from traditional Darcy's flow is positively correlated with the permeability. However, the width is not directly correlated with the relative aperture and the porosity.

13.
Trials ; 22(1): 576, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454591

RESUMO

BACKGROUND: Although catheter ablation is an effective therapy for atrial fibrillation (AF), the most common cardiac arrhythmia encountered in clinical practice, AF ablation generates inflammation and oxidative stress in the early postoperative period predisposing to recurrence of AF. Isolevuglandins (IsoLGs) are reactive lipid mediators of oxidative stress injury that rapidly react with endogenous biomolecules to compromise their function. 2-Hydroxybenzylamine (2-HOBA), a potent small molecule scavenger of IsoLGs, sequesters the reactive species as inert adducts. This mechanism, coupled with reported safety in humans, supports the investigation of 2-HOBA as a novel therapeutic to reduce AF caused by oxidative stress, such as that which occurs after catheter ablation. Accordingly, we seek to test the hypothesis that treatment with 2-HOBA will decrease early recurrence of AF and other atrial arrhythmias following AF ablation by decreasing IsoLG adducts with native biomolecules. METHODS: The proposed trial will randomly assign 162 participants undergoing cryo- or radiofrequency catheter ablation for AF to 2-HOBA (N = 81) or placebo (N = 81). Individuals will begin the study drug 3 days prior to ablation and continue for 28 days. Participants will be given a wearable smartwatch capable of detecting and recording atrial arrhythmias. They will be instructed to record ECGs daily with additional ECGs if they experience symptoms of AF or when alerted by the smartwatch AF detection alarm. The primary clinical endpoint will be an episode of AF, atrial tachycardia, or atrial flutter lasting 30 s or more within 28 days post-AF ablation. Secondary measures will be the change in IsoLG adduct levels from blood samples collected immediately pre-ablation and post-ablation and reduction in AF burden as calculated from the smartwatch. DISCUSSION: The proposed trial will test the hypothesis that 2-HOBA reduces post-ablation atrial arrhythmias through sequestration of reactive IsoLG species. The results of this study may improve the understanding of the role of IsoLGs and oxidative stress in AF pathogenesis and provide evidence to advance 2-HOBA and related compounds as a new therapeutic strategy to treat AF. TRIAL REGISTRATION: ClinicalTrials.gov NCT04433091 . Registered on June 3, 2020.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Preparações Farmacêuticas , Dispositivos Eletrônicos Vestíveis , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/prevenção & controle , Fibrilação Atrial/cirurgia , Benzilaminas , Ablação por Cateter/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
BMC Infect Dis ; 21(1): 774, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372792

RESUMO

BACKGROUND: The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19. METHODS: 172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models. Internal validation was performed by using bootstrap with 500 re-sampling in the training set, and external validation was performed in the validation set for the four models, respectively. RESULTS: Age, comorbidity, fever, and 18 laboratory markers were associated with the severity of COVID-19 (all P values < 0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914-0.943) and 0.827 (95% CI, 0.716-0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845-0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score. CONCLUSIONS: Eight clinical markers of lactate dehydrogenase, C-reactive protein, albumin, comorbidity, electrolyte disturbance, coagulation function, eosinophil and lymphocyte counts were associated with the severity of COVID-19. An assessment model constructed with these eight markers would help the clinician to evaluate the likelihood of developing severity of COVID-19 at admission and early take measures on clinical treatment.

15.
Environ Toxicol ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397165

RESUMO

In the present study, we aimed to evaluate the cardioprotective effect of neoandrographolide (Neo) on myocardial ischemia/reperfusion injury (I/R) models and explore its possible mechanism. We randomly and equally divided male mice into sham-operation, I/R, and I/R + Neo groups. H9C2 cell line and primary neonatal rat cardiomyocytes were induced into the simulated I/R's status and used to further validate the Neo's role in vitro. Heart systolic function, indexes of myocardial injury (IMI), infarct size, pathological change, cell apoptosis, inflammatory cytokines, and indexes related to apoptotic and NF-κB signaling pathways were analyzed in vivo or in vitro after the Neo treatment. Compared to the I/R group, Neo significantly suppressed IMI, infarct size, inflammatory cell infiltration, cell apoptosis, inflammatory cytokines, bax, cleaved caspase-3, P-IKBa, and P-NF-κB protein expressions, and the translocation of NF-kB subunit p65 from the cytoplasm to the nucleus in vivo or in vitro. Still, ejected fraction, fractional shortening, and the bcl-2 protein expression were notably increased after the Neo treatment. Neo could be developed into a new drug for treating myocardial I/R by inhibiting myocardial inflammation and apoptosis, which was closely related to suppressing the activation of bax/bcl-2 and NF-κB signaling pathways.

16.
J Cell Mol Med ; 25(18): 8920-8928, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34382339

RESUMO

Hypoxia as a crucial pathogenesis factor usually results in huge harmful effects on cardiac injury and dysfunction. Our previous study has uncovered the global transcriptome and translatome profiles of cardiomyocytes in vitro and in vivo to response to hypoxia by RNA sequencing and ribosome profiling sequencing. We observe a series of differential expressed genes between transcription and translation, which may be attributed to the hypoxia-specific binding affinity of nuclear cap-binding subunit 3 (NCBP3) at 5' untranslation region of target genes. Although we observe that NCBP3 can facilitate translational process in myocardium under hypoxia stress, the underlying molecular mechanism of NCBP3 for gene translation modulation remains unclear. In this study, we performed NCBP3 immunoprecipitation for mass spectrum and found that METTL3 and eIF4A2 particularly interacted with NCBP3 in hypoxic rat H9C2 cardiomyocytes. Furthermore, we observed that METTL3-mediated N6-methyladenosine (m6A) methylation was elevated in hypoxia, but compromised by NCBP3 or METTL3 knockdown. Finally, we also demonstrated that NCBP3/METTL3/eIF4A2 regulatory axis plays a specific role in cardiomyocytes undergoing hypoxic stress. Taken together, we unmasked NCBP3, a novel hypoxia-specific response protein functions as a scaffold to coordinate METTL3 and eIF4A2 for enhancing gene translation by m6A RNA methylation in cardiomyocytes upon hypoxic stress.

17.
Chin Med J (Engl) ; 134(17): 2048-2053, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34402479

RESUMO

BACKGROUND: With the ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, an increasing number of viral variants are being identified, which poses a challenge for nucleic acid-based diagnostic tests. Rapid tests, such as real-time reverse transcription-polymerase chain reaction (rRT-PCR), play an important role in monitoring COVID-19 infection and controlling its spread. However, the changes in the genotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in decreased sensitivity of the rRT-PCR assay and it is necessary to monitor the mutations in primers and probes of SARS-CoV-2 detection over time. METHODS: We developed two rRT-PCR assays to detect the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes of SARS-CoV-2. We evaluated these assays together with our previously published assays targeting the ORF1ab and N genes for the detection and confirmation of SARS-CoV-2 and its variants of concern (VOCs). In addition, we also developed two rRT-PCR assays (S484K and S501Y) targeting the spike gene, which when combined with the open reading frames (ORF)1ab assay, respectively, to form duplex rRT-PCR assays, were able to detect SARS-CoV-2 VOCs (lineages B.1.351 and B.1.1.7). RESULTS: Using a SARS-CoV-2 stock with predetermined genomic copies as a standard, the detection limit of both assays targeting RdRp and N was five copies/reaction. Furthermore, no cross-reactions with six others human CoVs (229E, OC43, NL63, HKU1, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus) were observed using these assays. In addition, the S484K and S501Y assays were combined with the ORF1ab assay, respectively. CONCLUSIONS: Four rRT-PCR assays (RdRp, N, S484K, and S501Y) were used to detect SARS-CoV-2 variants, and these assays were shown to be effective in screening for multiple virus strains.

18.
Mult Scler Relat Disord ; 55: 103188, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34371273

RESUMO

BACKGROUND: Delayed diagnosis and noneffective treatment contribute to the shorter life expectancy in patients with progressive multiple sclerosis (PMS). Studies demonstrate the key role of autoimmunity in PMS, but the prognostic value of immune-associated factors remains unknown. Thus, this study aimed to develop an immune-associated gene (IAG) signature related to overall survival (OS) and conduct an immune cell infiltration analysis using PMS data. METHODS: The differentially expressed IAGs were identified based on gene expression profiles (from the Gene Expression Omnibus database) and IAGs (from the ImmPort database). Univariate and least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analyses were used to develop the IAG signature related to OS. Kaplan-Meier analyses were conducted, and receiver operating characteristic (ROC) curves were generated to assess the performance. Additionally, the differential distribution of immune cells was identified by Wilcoxon rank-sum tests and correlations with IAGs were analyzed using Spearman correlation analyses. Moreover, univariate and multivariate Cox regression analyses were used to identify the independent prognostic factors to develop a prognostic nomogram. RESULTS: The training group, consisting of 57 PMS lesions and 52 control tissues, was obtained through batch normalization to remove the inter-batch difference. A total of 206 differentially expressed IAGs were identified, and 38 of them were associated with OS. Thereafter, a 4-IAG signature was constructed to calculate the risk score and thus classify PMS patients into high- and low-risk groups according to mean risk score. Patients in the high-risk group had a lower survival time than those in the low-risk group. The Kaplan-Meier plots and ROC curves demonstrated a good performance in both the training and internal validation groups. Additionally, five differentially abundant immune cell types were identified and their relationships with IAGs were analyzed. Finally, risk score, cortical region, and naive B cells were identified as independent prognostic factors, and a nomogram incorporating these factors was developed to predict the OS in PMS. CONCLUSION: The novel IAG signature may be a reliable tool for assisting neurologists in predicting the OS for PMS patients in clinical settings. These findings may facilitate personalized treatment and provide insights into the complex mechanism of PMS.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34382728

RESUMO

A direct and selective synthesis of α,ß-unsaturated piperidones by a new palladium-catalyzed cascade carbonylation is described. In the presented protocol, easily available propargylic alcohols react with aliphatic amines to provide a broad variety of interesting heterocycles. Key to the success of this transformation is a remarkable catalytic cleavage of the present carbon-carbon triple bond by using a specific catalyst with 2-diphenylphosphinopyridine as ligand and appropriate reaction conditions. Mechanistic studies and control experiments revealed branched unsaturated acid 11 as crucial intermediate.

20.
Int J Cancer ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34346504

RESUMO

Colorectal cancer is a leading cancer worldwide and in Vietnam. Adenomas (adenomatous polyps) is an important precursor of colorectal cancer. There is currently no study to determine the modifiable risk factors for colorectal adenomas, including body mass index (BMI) in Vietnam. We conducted an individually matched case-control study of 1149 colorectal adenomas and 1145 controls in a large-scale colorectal screening program involving 103 542 individuals aged 40-75 years old in Hanoi, Vietnam. Conditional logistic regression was used to evaluate the association between BMI and colorectal adenomas prevalence, after controlling for potential confounders. Overall, comparing to normal weight (ie, 18.5-22.9 kg/m2 ), underweight (ie, BMI < 18.5) was associated with a non-statistically significant increased prevalence of colorectal adenomas (odd ratio [OR] = 1.29 and 95% confident interval [CI]: 0.88-1.87). This association became significant among male (OR = 1.98, 95% CI: 1.20-3.27), male who were ever smokers (OR = 2.59, 95% CI: 1.33-5.03), nonregular exercise (OR = 2.44, 95% CI: 1.26-4.73) and individuals with cardiometabolic disorders (OR = 3.46, 95% CI: 1.19-10.00). The association between underweight and colorectal adenomas did not vary by smoking status, drinking status, family history of cancer, adenomas types or cardiometabolic disorders. No association was observed among obese individuals (BMI ≥ 25). In the population with low prevalence of obesity, we found that the association between BMI and colorectal adenomas followed a reversed J-shape that underweight was associated with increased prevalence. Further studies are, therefore, warranted to replicate our results and to investigate the biologic mechanism the effect of underweight on colorectal adenomas prevalence.

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